Intra-tumoural regulatory T cells: A potential new target in cancer immunotherapy

We hypothesised that T reg cells preferentially expand/infiltrate inside murine mesotheliomas. Immunotherapy based on the manipulation of T reg cell populations should therefore be targeted to the tumour site. The AE17 murine mesothelioma model was used for this study. Both intra-tumoural T reg cells and those in the periphery of tumour-bearing mice were identified by flow cytometry. The effect on tumour growth of intra-tumoural depletion of T reg cells using the PC61 anti-CD25 mAb was then examined. We identified CD4 + T reg cells co-expressing both the CD25 cell surface marker and the transcription factor Foxp3 within murine mesotheliomas. These intra-tumoural T reg cells increase significantly as a percentage of total CD4 + T cells within the tumour as it grows. We showed that the depletion of intra-tumoural T reg cells with anti-CD25 mAb injected directly into the tumours can cause significantly reduced tumour growth. Localised, intra-tumoural depletion of T reg cells is a new, clinically relevant treatment option for established tumours.